ICYMI Multiple Sclerosis

womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.

Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.

Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.

In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).

After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.

In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).

“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.

[email protected]

SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.


 

womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.

Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.

Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.

In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).

After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.

In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).

“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.

[email protected]

SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.


 

womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.

Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.

Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.

In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).

After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.

In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).

“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.

[email protected]

SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.


 

WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.

“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.

The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.

“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”

While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.

For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.

They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).

In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).

A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).

The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).

The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).

And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).

“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.

“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”

Early menopause also linked to shorter progression to secondary progressive MS

The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).

The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).

The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.

“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.

Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).

Possible mechanisms and applications of the findings

The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.

“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.

“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.

The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.

“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.

“However, our study ultimately may lead to such a trial.”

In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.

“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”

Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”

“More studies are needed in this important issue in a disease that affects women three times more than men.”

Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.

WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.

“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.

The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.

“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”

While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.

For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.

They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).

In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).

A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).

The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).

The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).

And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).

“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.

“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”

Early menopause also linked to shorter progression to secondary progressive MS

The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).

The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).

The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.

“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.

Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).

Possible mechanisms and applications of the findings

The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.

“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.

“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.

The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.

“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.

“However, our study ultimately may lead to such a trial.”

In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.

“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”

Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”

“More studies are needed in this important issue in a disease that affects women three times more than men.”

Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.

WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.

“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.

The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.

“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”

While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.

For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.

They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).

In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).

A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).

The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).

The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).

And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).

“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.

“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”

Early menopause also linked to shorter progression to secondary progressive MS

The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).

The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).

The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.

“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.

Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).

Possible mechanisms and applications of the findings

The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.

“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.

“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.

The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.

“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.

“However, our study ultimately may lead to such a trial.”

In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.

“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”

Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”

“More studies are needed in this important issue in a disease that affects women three times more than men.”

Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.

WEST PALM BEACH, FLA. – Baseline measurements of the eye may help neurologists predict future disease activity and diagnosis after the first attack of clinically isolated syndrome (CIS), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that optical coherence tomography (OCT) could support patient monitoring and the initiation of disease-modifying therapy.

“Treatment of early MS [multiple sclerosis] is crucial to prevent neuroaxonal damage and, thus, sustained disability,” said Hanna G. Zimmermann, PhD, a research associate at NeuroCure Clinical Research Center at Charité Universitätsmedizin in Berlin. The ability to identify patients at high risk of future disease activity shortly after disease onset could help optimize patient management and guide the initiation of disease-modifying therapy. Dr. Zimmermann and colleagues investigated whether retinal OCT could predict disease activity in patients with CIS.

The investigators included 97 patients (mean age, 33.6 years; 62.9% female) with CIS in a prospective, longitudinal cohort study. Diagnoses of CIS were based on the 2010 revisions to the McDonald criteria. Patients were enrolled from two German centers within 12 months after a first clinical event. The researchers performed a neurologic examination, cerebral MRI, and retinal OCT for each participant and followed the population for 729 days (median, 664 days).

The primary OCT predictor was ganglion cell and inner plexiform (GCIP) layer thickness, because this parameter is stable and reliable for quantifying neuronal visual system damage in MS, said Dr. Zimmermann. Secondary OCT predictors were peripapillary retinal nerve fiber layer (pRNFL) thickness and inner nuclear layer (INL) thickness. The investigators only included eyes without a history of optic neuritis in the analysis.

The study’s primary outcome was failing the no evidence of disease activity (NEDA-3) criteria (no relapses, no disability progression, and no MRI activity). The secondary outcomes were MS diagnosis (according to the 2010 McDonald criteria) and worsening of disability.

At baseline, Dr. Zimmerman and colleagues found no differences in thickness of GCIP and pRNFL between patients and matched healthy controls. In all, 58 patients (59%) failed NEDA-3 criteria during follow-up. When Dr. Zimmermann and colleagues conducted Kaplan-Meier analysis, they found that patients with thinner GCIP thickness had a significantly higher risk of failing NEDA-3 criteria (thinnest vs. thickest tertile: hazard ratio, 3.33). A follow-up diagnosis of MS also was significantly more likely among patients with low GCIP thickness (thinnest vs. thickest tertile: HR, 4.05).

In addition, low pRNFL thickness indicated an increased risk of not meeting NEDA-3 criteria (thinnest vs. thickest tertile: HR, 2.46). However, neither INL thickness nor T2-weighted lesion count were associated with failing NEDA-3 criteria. Also, none of the OCT parameters were associated with future disability worsening.

Among the study’s limitations are its small sample size, the relatively short observation time, and the heterogeneity of patients between the two centers, which used different study protocols, said Dr. Zimmermann.

“OCT-assessed GCIP is promising for the early appraisal of future disease activity and might thus be helpful for risk-adjusted patient participation in clinical research,” she said. “It might also be helpful for clinicians for identifying CIS patients with worse prognosis and planning the care.” Dr. Zimmermann and colleagues plan to use advanced imaging techniques in future studies to understand the mechanisms behind the associations they identified. They hope to confirm their findings in a larger cohort and examine whether OCT can predict clinical outcomes such as relapses, disability worsening, and the extent of disease activity.

Dr. Zimmermann had no relevant disclosures and did not report a source of funding for the study.

[email protected]

SOURCE: Zimmermann HG et al. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Baseline measurements of the eye may help neurologists predict future disease activity and diagnosis after the first attack of clinically isolated syndrome (CIS), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that optical coherence tomography (OCT) could support patient monitoring and the initiation of disease-modifying therapy.

“Treatment of early MS [multiple sclerosis] is crucial to prevent neuroaxonal damage and, thus, sustained disability,” said Hanna G. Zimmermann, PhD, a research associate at NeuroCure Clinical Research Center at Charité Universitätsmedizin in Berlin. The ability to identify patients at high risk of future disease activity shortly after disease onset could help optimize patient management and guide the initiation of disease-modifying therapy. Dr. Zimmermann and colleagues investigated whether retinal OCT could predict disease activity in patients with CIS.

The investigators included 97 patients (mean age, 33.6 years; 62.9% female) with CIS in a prospective, longitudinal cohort study. Diagnoses of CIS were based on the 2010 revisions to the McDonald criteria. Patients were enrolled from two German centers within 12 months after a first clinical event. The researchers performed a neurologic examination, cerebral MRI, and retinal OCT for each participant and followed the population for 729 days (median, 664 days).

The primary OCT predictor was ganglion cell and inner plexiform (GCIP) layer thickness, because this parameter is stable and reliable for quantifying neuronal visual system damage in MS, said Dr. Zimmermann. Secondary OCT predictors were peripapillary retinal nerve fiber layer (pRNFL) thickness and inner nuclear layer (INL) thickness. The investigators only included eyes without a history of optic neuritis in the analysis.

The study’s primary outcome was failing the no evidence of disease activity (NEDA-3) criteria (no relapses, no disability progression, and no MRI activity). The secondary outcomes were MS diagnosis (according to the 2010 McDonald criteria) and worsening of disability.

At baseline, Dr. Zimmerman and colleagues found no differences in thickness of GCIP and pRNFL between patients and matched healthy controls. In all, 58 patients (59%) failed NEDA-3 criteria during follow-up. When Dr. Zimmermann and colleagues conducted Kaplan-Meier analysis, they found that patients with thinner GCIP thickness had a significantly higher risk of failing NEDA-3 criteria (thinnest vs. thickest tertile: hazard ratio, 3.33). A follow-up diagnosis of MS also was significantly more likely among patients with low GCIP thickness (thinnest vs. thickest tertile: HR, 4.05).

In addition, low pRNFL thickness indicated an increased risk of not meeting NEDA-3 criteria (thinnest vs. thickest tertile: HR, 2.46). However, neither INL thickness nor T2-weighted lesion count were associated with failing NEDA-3 criteria. Also, none of the OCT parameters were associated with future disability worsening.

Among the study’s limitations are its small sample size, the relatively short observation time, and the heterogeneity of patients between the two centers, which used different study protocols, said Dr. Zimmermann.

“OCT-assessed GCIP is promising for the early appraisal of future disease activity and might thus be helpful for risk-adjusted patient participation in clinical research,” she said. “It might also be helpful for clinicians for identifying CIS patients with worse prognosis and planning the care.” Dr. Zimmermann and colleagues plan to use advanced imaging techniques in future studies to understand the mechanisms behind the associations they identified. They hope to confirm their findings in a larger cohort and examine whether OCT can predict clinical outcomes such as relapses, disability worsening, and the extent of disease activity.

Dr. Zimmermann had no relevant disclosures and did not report a source of funding for the study.

[email protected]

SOURCE: Zimmermann HG et al. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Baseline measurements of the eye may help neurologists predict future disease activity and diagnosis after the first attack of clinically isolated syndrome (CIS), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that optical coherence tomography (OCT) could support patient monitoring and the initiation of disease-modifying therapy.

“Treatment of early MS [multiple sclerosis] is crucial to prevent neuroaxonal damage and, thus, sustained disability,” said Hanna G. Zimmermann, PhD, a research associate at NeuroCure Clinical Research Center at Charité Universitätsmedizin in Berlin. The ability to identify patients at high risk of future disease activity shortly after disease onset could help optimize patient management and guide the initiation of disease-modifying therapy. Dr. Zimmermann and colleagues investigated whether retinal OCT could predict disease activity in patients with CIS.

The investigators included 97 patients (mean age, 33.6 years; 62.9% female) with CIS in a prospective, longitudinal cohort study. Diagnoses of CIS were based on the 2010 revisions to the McDonald criteria. Patients were enrolled from two German centers within 12 months after a first clinical event. The researchers performed a neurologic examination, cerebral MRI, and retinal OCT for each participant and followed the population for 729 days (median, 664 days).

The primary OCT predictor was ganglion cell and inner plexiform (GCIP) layer thickness, because this parameter is stable and reliable for quantifying neuronal visual system damage in MS, said Dr. Zimmermann. Secondary OCT predictors were peripapillary retinal nerve fiber layer (pRNFL) thickness and inner nuclear layer (INL) thickness. The investigators only included eyes without a history of optic neuritis in the analysis.

The study’s primary outcome was failing the no evidence of disease activity (NEDA-3) criteria (no relapses, no disability progression, and no MRI activity). The secondary outcomes were MS diagnosis (according to the 2010 McDonald criteria) and worsening of disability.

At baseline, Dr. Zimmerman and colleagues found no differences in thickness of GCIP and pRNFL between patients and matched healthy controls. In all, 58 patients (59%) failed NEDA-3 criteria during follow-up. When Dr. Zimmermann and colleagues conducted Kaplan-Meier analysis, they found that patients with thinner GCIP thickness had a significantly higher risk of failing NEDA-3 criteria (thinnest vs. thickest tertile: hazard ratio, 3.33). A follow-up diagnosis of MS also was significantly more likely among patients with low GCIP thickness (thinnest vs. thickest tertile: HR, 4.05).

In addition, low pRNFL thickness indicated an increased risk of not meeting NEDA-3 criteria (thinnest vs. thickest tertile: HR, 2.46). However, neither INL thickness nor T2-weighted lesion count were associated with failing NEDA-3 criteria. Also, none of the OCT parameters were associated with future disability worsening.

Among the study’s limitations are its small sample size, the relatively short observation time, and the heterogeneity of patients between the two centers, which used different study protocols, said Dr. Zimmermann.

“OCT-assessed GCIP is promising for the early appraisal of future disease activity and might thus be helpful for risk-adjusted patient participation in clinical research,” she said. “It might also be helpful for clinicians for identifying CIS patients with worse prognosis and planning the care.” Dr. Zimmermann and colleagues plan to use advanced imaging techniques in future studies to understand the mechanisms behind the associations they identified. They hope to confirm their findings in a larger cohort and examine whether OCT can predict clinical outcomes such as relapses, disability worsening, and the extent of disease activity.

Dr. Zimmermann had no relevant disclosures and did not report a source of funding for the study.

[email protected]

SOURCE: Zimmermann HG et al. ACTRIMS Forum 2020, Abstract.

Key clinical point: Lower amyloid positron imaging tomography (PET) uptake in normal-appearing white matter (NAWM) is associated with cognitive decline and an increase in white matter lesion volume.

Major finding: Cognitive decline was associated with lower standardized uptake value relative to cerebellum in NAWM (1.52 in the cognitive decline group vs. 1.67 in the cognitively stable group; Mann-Whitney U test [U] = 42.0; P = .011), lower thalamic volume (13.84 vs. 15.61; U = 55.0; P = .059), and higher white matter lesion burden (15.25 vs. 9.17; U = 49.0; P = .029).

Study details: A prospective longitudinal PET study using 18F-florbetaben included 29 patients diagnosed with MS; the mean follow-up period was 18.00 ± 3.31 months.

Disclosures: The authors declared no conflicts of interest.

Citation: Pytel V et al. Mult Scler Relat Disord. 2020 Jan 2. doi: 10.1016/j.msard.2020.101926. 

Key clinical point: Lower amyloid positron imaging tomography (PET) uptake in normal-appearing white matter (NAWM) is associated with cognitive decline and an increase in white matter lesion volume.

Major finding: Cognitive decline was associated with lower standardized uptake value relative to cerebellum in NAWM (1.52 in the cognitive decline group vs. 1.67 in the cognitively stable group; Mann-Whitney U test [U] = 42.0; P = .011), lower thalamic volume (13.84 vs. 15.61; U = 55.0; P = .059), and higher white matter lesion burden (15.25 vs. 9.17; U = 49.0; P = .029).

Study details: A prospective longitudinal PET study using 18F-florbetaben included 29 patients diagnosed with MS; the mean follow-up period was 18.00 ± 3.31 months.

Disclosures: The authors declared no conflicts of interest.

Citation: Pytel V et al. Mult Scler Relat Disord. 2020 Jan 2. doi: 10.1016/j.msard.2020.101926. 

Key clinical point: Lower amyloid positron imaging tomography (PET) uptake in normal-appearing white matter (NAWM) is associated with cognitive decline and an increase in white matter lesion volume.

Major finding: Cognitive decline was associated with lower standardized uptake value relative to cerebellum in NAWM (1.52 in the cognitive decline group vs. 1.67 in the cognitively stable group; Mann-Whitney U test [U] = 42.0; P = .011), lower thalamic volume (13.84 vs. 15.61; U = 55.0; P = .059), and higher white matter lesion burden (15.25 vs. 9.17; U = 49.0; P = .029).

Study details: A prospective longitudinal PET study using 18F-florbetaben included 29 patients diagnosed with MS; the mean follow-up period was 18.00 ± 3.31 months.

Disclosures: The authors declared no conflicts of interest.

Citation: Pytel V et al. Mult Scler Relat Disord. 2020 Jan 2. doi: 10.1016/j.msard.2020.101926. 

Key clinical point: Mothers of children with MS are more likely to use mental health services before and after their child’s diagnosis with multiple sclerosis (MS) than mothers of children without MS.

Major finding: The prevalence of any physical condition and mood or anxiety disorder was higher in MS-mothers vs. non-MS-mothers. The odds of having any psychiatry visit was significantly increased in MS-mothers (odds ratio, 1.60; 95% confidence interval [CI], 1.10-2.31). The annual rate of psychiatry visits did not differ between MS-mothers and non-MS-mothers (rate ratio, 0.66; 95% CI, 0.33-1.30).

Study details: A population-based retrospective matched cohort study of 156 MS-mothers and 624 non-MS mothers.

Disclosures: This study was funded by the Multiple Sclerosis Scientific Research Foundation. Dr. Marrie received research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, and CMSC and was supported by the Waugh Family Chair in Multiple Sclerosis.

Citation: Marrie RA et al. Neurology. 2020 Jan 9. doi: 10.1212/WNL.0000000000008871. 

Key clinical point: Mothers of children with MS are more likely to use mental health services before and after their child’s diagnosis with multiple sclerosis (MS) than mothers of children without MS.

Major finding: The prevalence of any physical condition and mood or anxiety disorder was higher in MS-mothers vs. non-MS-mothers. The odds of having any psychiatry visit was significantly increased in MS-mothers (odds ratio, 1.60; 95% confidence interval [CI], 1.10-2.31). The annual rate of psychiatry visits did not differ between MS-mothers and non-MS-mothers (rate ratio, 0.66; 95% CI, 0.33-1.30).

Study details: A population-based retrospective matched cohort study of 156 MS-mothers and 624 non-MS mothers.

Disclosures: This study was funded by the Multiple Sclerosis Scientific Research Foundation. Dr. Marrie received research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, and CMSC and was supported by the Waugh Family Chair in Multiple Sclerosis.

Citation: Marrie RA et al. Neurology. 2020 Jan 9. doi: 10.1212/WNL.0000000000008871. 

Key clinical point: Mothers of children with MS are more likely to use mental health services before and after their child’s diagnosis with multiple sclerosis (MS) than mothers of children without MS.

Major finding: The prevalence of any physical condition and mood or anxiety disorder was higher in MS-mothers vs. non-MS-mothers. The odds of having any psychiatry visit was significantly increased in MS-mothers (odds ratio, 1.60; 95% confidence interval [CI], 1.10-2.31). The annual rate of psychiatry visits did not differ between MS-mothers and non-MS-mothers (rate ratio, 0.66; 95% CI, 0.33-1.30).

Study details: A population-based retrospective matched cohort study of 156 MS-mothers and 624 non-MS mothers.

Disclosures: This study was funded by the Multiple Sclerosis Scientific Research Foundation. Dr. Marrie received research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, and CMSC and was supported by the Waugh Family Chair in Multiple Sclerosis.

Citation: Marrie RA et al. Neurology. 2020 Jan 9. doi: 10.1212/WNL.0000000000008871. 

Key clinical point: Vitamin D and body mass index (BMI) are independent causal risk factors for multiple sclerosis (MS) in adulthood and childhood.

Major finding: Genetically determined increased childhood BMI and adult BMI were associated with a 24% and 14% higher risk of MS, respectively. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% reduction in the MS risk. 

Study details: A 2-sample Mendelian randomization study estimated the effect of BMI and vitamin D status on MS risk; associations of single-nucleotide polymorphisms with both the risk factors of interest were obtained from the relevant consortia.

Disclosures: This study was funded through a grant from the Barts Charity. The authors declared no conflicts of interest.

Citation: Jacobs BM et al. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 14. doi: 10.1212/NXI.0000000000000662. 

Key clinical point: Vitamin D and body mass index (BMI) are independent causal risk factors for multiple sclerosis (MS) in adulthood and childhood.

Major finding: Genetically determined increased childhood BMI and adult BMI were associated with a 24% and 14% higher risk of MS, respectively. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% reduction in the MS risk. 

Study details: A 2-sample Mendelian randomization study estimated the effect of BMI and vitamin D status on MS risk; associations of single-nucleotide polymorphisms with both the risk factors of interest were obtained from the relevant consortia.

Disclosures: This study was funded through a grant from the Barts Charity. The authors declared no conflicts of interest.

Citation: Jacobs BM et al. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 14. doi: 10.1212/NXI.0000000000000662. 

Key clinical point: Vitamin D and body mass index (BMI) are independent causal risk factors for multiple sclerosis (MS) in adulthood and childhood.

Major finding: Genetically determined increased childhood BMI and adult BMI were associated with a 24% and 14% higher risk of MS, respectively. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% reduction in the MS risk. 

Study details: A 2-sample Mendelian randomization study estimated the effect of BMI and vitamin D status on MS risk; associations of single-nucleotide polymorphisms with both the risk factors of interest were obtained from the relevant consortia.

Disclosures: This study was funded through a grant from the Barts Charity. The authors declared no conflicts of interest.

Citation: Jacobs BM et al. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 14. doi: 10.1212/NXI.0000000000000662. 

Key clinical point: In patients with multiple sclerosis (MS) without good recovery after the initial relapse, initiating a disease-modifying therapy (DMT) immediately increases the likelihood of a benign disease course.

Major finding: Patients with good recovery and immediate DMT initiation and those with poor recovery and delayed DMT initiation had about 65% and 20% chance, respectively, of remaining at a minimal disability level (Expanded Disability Status Scale score of less than 2.5) by age 45 years.

Study details: An analysis of data from the phase 3 CHAMPS trial in clinically isolated syndrome (n=383) and 10-year follow-up EXTENSION trial.

Disclosures: This study was funded by an unrestricted grant to Dr. Kantarci from Biogen. Dr. Kantarci and Dr. Atkinson received salary support as part of the grant from Biogen. Dr. Castrillo-Viguera was employed by Biogen.

Citation: Kantarci OH et al. Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17. doi: 10.1212/NXI.0000000000000653. 

Key clinical point: In patients with multiple sclerosis (MS) without good recovery after the initial relapse, initiating a disease-modifying therapy (DMT) immediately increases the likelihood of a benign disease course.

Major finding: Patients with good recovery and immediate DMT initiation and those with poor recovery and delayed DMT initiation had about 65% and 20% chance, respectively, of remaining at a minimal disability level (Expanded Disability Status Scale score of less than 2.5) by age 45 years.

Study details: An analysis of data from the phase 3 CHAMPS trial in clinically isolated syndrome (n=383) and 10-year follow-up EXTENSION trial.

Disclosures: This study was funded by an unrestricted grant to Dr. Kantarci from Biogen. Dr. Kantarci and Dr. Atkinson received salary support as part of the grant from Biogen. Dr. Castrillo-Viguera was employed by Biogen.

Citation: Kantarci OH et al. Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17. doi: 10.1212/NXI.0000000000000653. 

Key clinical point: In patients with multiple sclerosis (MS) without good recovery after the initial relapse, initiating a disease-modifying therapy (DMT) immediately increases the likelihood of a benign disease course.

Major finding: Patients with good recovery and immediate DMT initiation and those with poor recovery and delayed DMT initiation had about 65% and 20% chance, respectively, of remaining at a minimal disability level (Expanded Disability Status Scale score of less than 2.5) by age 45 years.

Study details: An analysis of data from the phase 3 CHAMPS trial in clinically isolated syndrome (n=383) and 10-year follow-up EXTENSION trial.

Disclosures: This study was funded by an unrestricted grant to Dr. Kantarci from Biogen. Dr. Kantarci and Dr. Atkinson received salary support as part of the grant from Biogen. Dr. Castrillo-Viguera was employed by Biogen.

Citation: Kantarci OH et al. Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17. doi: 10.1212/NXI.0000000000000653. 

Key clinical point: Phase 3 EVOLVE-MS-2 study demonstrates that diroximel fumarate (DRF) has an improved gastrointestinal (GI) tolerability profile compared with dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS).

Major finding: Patients treated with DRF self-reported 46% fewer days with an Individual Gastrointestinal Symptom and Impact Scale (IGISIS) symptom intensity score of ≥2 vs those treated with DMF (rate ratio, 0.54; 95% confidence interval, 0.39-0.75). The rates of GI adverse events (AEs) were lower with DRF than DMF (34.8% vs. 49.0%). DRF-treated patients had a lower discontinuation rate because of GI AEs (0.8% vs. 4.8%) and overall AEs (1.6% vs. 5.6%).

Study details: EVOLVE-MS-2 was a 5-week randomized trial that directly compared the GI tolerability of DRF 462 mg (n = 253) with that of DMF 240 mg (n = 249); primary endpoint was the number of days with an IGISIS intensity score of 2 or greater relative to exposure.

Disclosures: This study was funded by Alkermes Inc. and Biogen. The authors reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Naismith RT et al. CNS Drugs. 2020 Jan 17. doi: 10.1007/s40263-020-00700-0. 

Key clinical point: Phase 3 EVOLVE-MS-2 study demonstrates that diroximel fumarate (DRF) has an improved gastrointestinal (GI) tolerability profile compared with dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS).

Major finding: Patients treated with DRF self-reported 46% fewer days with an Individual Gastrointestinal Symptom and Impact Scale (IGISIS) symptom intensity score of ≥2 vs those treated with DMF (rate ratio, 0.54; 95% confidence interval, 0.39-0.75). The rates of GI adverse events (AEs) were lower with DRF than DMF (34.8% vs. 49.0%). DRF-treated patients had a lower discontinuation rate because of GI AEs (0.8% vs. 4.8%) and overall AEs (1.6% vs. 5.6%).

Study details: EVOLVE-MS-2 was a 5-week randomized trial that directly compared the GI tolerability of DRF 462 mg (n = 253) with that of DMF 240 mg (n = 249); primary endpoint was the number of days with an IGISIS intensity score of 2 or greater relative to exposure.

Disclosures: This study was funded by Alkermes Inc. and Biogen. The authors reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Naismith RT et al. CNS Drugs. 2020 Jan 17. doi: 10.1007/s40263-020-00700-0. 

Key clinical point: Phase 3 EVOLVE-MS-2 study demonstrates that diroximel fumarate (DRF) has an improved gastrointestinal (GI) tolerability profile compared with dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS).

Major finding: Patients treated with DRF self-reported 46% fewer days with an Individual Gastrointestinal Symptom and Impact Scale (IGISIS) symptom intensity score of ≥2 vs those treated with DMF (rate ratio, 0.54; 95% confidence interval, 0.39-0.75). The rates of GI adverse events (AEs) were lower with DRF than DMF (34.8% vs. 49.0%). DRF-treated patients had a lower discontinuation rate because of GI AEs (0.8% vs. 4.8%) and overall AEs (1.6% vs. 5.6%).

Study details: EVOLVE-MS-2 was a 5-week randomized trial that directly compared the GI tolerability of DRF 462 mg (n = 253) with that of DMF 240 mg (n = 249); primary endpoint was the number of days with an IGISIS intensity score of 2 or greater relative to exposure.

Disclosures: This study was funded by Alkermes Inc. and Biogen. The authors reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Naismith RT et al. CNS Drugs. 2020 Jan 17. doi: 10.1007/s40263-020-00700-0. 

Key clinical point: Ozanimod has a superior benefit-risk profile compared with fingolimod for the treatment of relapsing multiple sclerosis (RMS).

Major finding: Compared with fingolimod, ozanimod was associated with lower rates of conduction abnormalities (risk difference, −3.5%) and first-degree atrioventricular block (risk difference, −3.0%), lower risk of extended first-dose cardiac monitoring, and lower risk of adverse events over 1-2 years of follow-up. Efficacy outcomes were comparable.

Study details: Using a matching-adjusted indirect comparison, the first-dose cardiac monitoring outcomes and 1- and 2-year safety and efficacy outcomes were compared for ozanimod and fingolimod in patients with RMS.

Disclosures: The study received research support from Celgene, a wholly-owned subsidiary of Bristol-Myers Squibb. Five authors are employees of Bristol-Myers Squibb. Four authors are employees of Analysis Group, Inc., who have received consulting fees from Bristol-Myers Squibb.

Citation: Swallow E et al. J Comp Eff Res. 2020 Jan 17. doi: 10.2217/cer-2019-0169.

Key clinical point: Ozanimod has a superior benefit-risk profile compared with fingolimod for the treatment of relapsing multiple sclerosis (RMS).

Major finding: Compared with fingolimod, ozanimod was associated with lower rates of conduction abnormalities (risk difference, −3.5%) and first-degree atrioventricular block (risk difference, −3.0%), lower risk of extended first-dose cardiac monitoring, and lower risk of adverse events over 1-2 years of follow-up. Efficacy outcomes were comparable.

Study details: Using a matching-adjusted indirect comparison, the first-dose cardiac monitoring outcomes and 1- and 2-year safety and efficacy outcomes were compared for ozanimod and fingolimod in patients with RMS.

Disclosures: The study received research support from Celgene, a wholly-owned subsidiary of Bristol-Myers Squibb. Five authors are employees of Bristol-Myers Squibb. Four authors are employees of Analysis Group, Inc., who have received consulting fees from Bristol-Myers Squibb.

Citation: Swallow E et al. J Comp Eff Res. 2020 Jan 17. doi: 10.2217/cer-2019-0169.

Key clinical point: Ozanimod has a superior benefit-risk profile compared with fingolimod for the treatment of relapsing multiple sclerosis (RMS).

Major finding: Compared with fingolimod, ozanimod was associated with lower rates of conduction abnormalities (risk difference, −3.5%) and first-degree atrioventricular block (risk difference, −3.0%), lower risk of extended first-dose cardiac monitoring, and lower risk of adverse events over 1-2 years of follow-up. Efficacy outcomes were comparable.

Study details: Using a matching-adjusted indirect comparison, the first-dose cardiac monitoring outcomes and 1- and 2-year safety and efficacy outcomes were compared for ozanimod and fingolimod in patients with RMS.

Disclosures: The study received research support from Celgene, a wholly-owned subsidiary of Bristol-Myers Squibb. Five authors are employees of Bristol-Myers Squibb. Four authors are employees of Analysis Group, Inc., who have received consulting fees from Bristol-Myers Squibb.

Citation: Swallow E et al. J Comp Eff Res. 2020 Jan 17. doi: 10.2217/cer-2019-0169.

Key clinical point: Polypharmacy is common in patients with multiple sclerosis (MS) and is negatively associated with health outcomes.

Major finding: The rates of polypharmacy among patients with MS ranged from 14.9% to 59% across the studies that were reviewed. Polypharmacy was significantly associated with increased hospitalization rates, cognitive deficits, fatigue, higher relapse rates, and a lower quality of life, particularly among elderly patients.

Study details: The data come from a qualitative systematic review of 7 studies.  

Disclosures: Niklas Frahm has received travel funds for research meetings from Novartis. Michael Hecker received speaking fees and travel funds from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva. Uwe Klaus Zettl received research support and lecture fees or travel funds from Almirall, Alexion, Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva.

Citation: Frahm N et al. Expert Opin Drug Saf. 2020 Jan 27. doi: 10.1080/14740338.2020.1720646.

Key clinical point: Polypharmacy is common in patients with multiple sclerosis (MS) and is negatively associated with health outcomes.

Major finding: The rates of polypharmacy among patients with MS ranged from 14.9% to 59% across the studies that were reviewed. Polypharmacy was significantly associated with increased hospitalization rates, cognitive deficits, fatigue, higher relapse rates, and a lower quality of life, particularly among elderly patients.

Study details: The data come from a qualitative systematic review of 7 studies.  

Disclosures: Niklas Frahm has received travel funds for research meetings from Novartis. Michael Hecker received speaking fees and travel funds from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva. Uwe Klaus Zettl received research support and lecture fees or travel funds from Almirall, Alexion, Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva.

Citation: Frahm N et al. Expert Opin Drug Saf. 2020 Jan 27. doi: 10.1080/14740338.2020.1720646.

Key clinical point: Polypharmacy is common in patients with multiple sclerosis (MS) and is negatively associated with health outcomes.

Major finding: The rates of polypharmacy among patients with MS ranged from 14.9% to 59% across the studies that were reviewed. Polypharmacy was significantly associated with increased hospitalization rates, cognitive deficits, fatigue, higher relapse rates, and a lower quality of life, particularly among elderly patients.

Study details: The data come from a qualitative systematic review of 7 studies.  

Disclosures: Niklas Frahm has received travel funds for research meetings from Novartis. Michael Hecker received speaking fees and travel funds from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva. Uwe Klaus Zettl received research support and lecture fees or travel funds from Almirall, Alexion, Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva.

Citation: Frahm N et al. Expert Opin Drug Saf. 2020 Jan 27. doi: 10.1080/14740338.2020.1720646.